Loganic Acid Methyltransferase: Insights into the Specificity of Methylation on an Iridoid Glycoside

Loganin is an iridoid glycoside of interest as both an intermediate in the biosynthesis of indole alkaloids in plants and as a bioactive compound itself. Loganic acid methyltransferase catalyzes the methylation of a monoterpenoid glycoside precursor to produce loganin and demonstrates stereospecificity for the (6S,7R) substrate. We have biochemically characterized this biocatalyst and elucidated the basis for its strict substrate specificity. These studies could help facilitate the design of new classes of monoterpenoid indole alkaloids of pharmaceutical interest. Reading the crystal ball: The crystal structure of loganic acid O‐methyltransferase from Catharanthus roseus (CrLAMT) revealed how the enzyme has evolved for methylation of a large glycosylated substrate. It also shed light on the molecular basis for the enzyme's high specificity towards a glycosylated and hydroxylated iridoid ring.